2.1. Anti-Idiotypic Antibodies
Anti-idiotypic antibodies or anti-idiotypes are antibodies directed against the antigen-combining region or variable region (called the idiotype) of another antibody molecule. In theory, based on Jerne's network model of idiotypic relationships (Jerne, N. K., 1974, Ann. Immunol. (Paris) 125c:373; Jerne, N. K., et al., 1982, EMBO 1:234), immunization with an antibody molecule expressing a paratope (antigen-combining site) for a given antigen should produce a group of anti-antibodies, some of which share with the antigen a complementary structure to the paratope. Immunization with a subpopulation of the anti-idiotypic antibodies should in turn produce a subpopulation of antibodies or immune cell subsets that are reactive to the initial antigen.
A network of idiotopes and anti-idiotopes has been invoked to explain immune regulation, with common or related idiotopes of antibodies, B lymphocytes, and various subsets of T lymphocytes and their soluble products interacting with anti-idiotopes (Jerne, N. K., 1974, Supra; Urbain, J., et al., 1977, Proc. Natl. Acad. Sci. U.S.A. 74:5126; Rajewski, R. and Takemori, T., 1983, Ann. Rev. Immunol. 1:569). Studies which have been done on immunity to both haptens and vital antigens indicate that B cell derived anti-idiotypic antibodies can induce T cell responses (RaJewski, R. and Takemori, T., Supra; Urbain, J., et al., supra; Binz, H. and Wigzell, H., 1978, J. Exp. Med. 147:63). For example, Ertl et al. immunized mice with a Sendal virus-specific T cell clone and produced an anti-idiotypic mAb which regulated the DTH response to Sendai virus (Ertl, H. C. J., et al., 1982, Proc. Natl. Acad. Sci. U.S.A. 79:7479). As evidence for a B cell antibody arising in response to a T cell idiotope, Kennedy et al. observed tumor rejection, but no antitumor antibodies, in mice treated with anti-idiotopic antibodies relating to the SV40 T antigen (Kennedy, R. C., et al., 1985, J. Exp. Med. 161:1432). The administration of exogenous anti-idiotypic antibody can exert enhancing or suppressive influences, dependent on, among other variables, the dose of the antibody (Reth, M., et al., 1981, Nature (London) 290:257).